P. aeruginosa is originally known as an attenuated pathogenic bacterium. In accordance with the recent increase in the rate of occurrence of bacterial replacement and proliferation resulting from the administration of large doses of antibiotics, the number of patients infected by P. aeruginosa as distinct from other bacterial infectious diseases has notably increased.
P. aeruginosa easily causes infectious disease in patients having reduced resistance to infection, and therefore this infectious disease is one of the representative opportunistic infectious diseases. The above patients having reduced resistance to infection include patients with cancer, those receiving immunosuppressive therapy, implantation patients, burn patients, and infants.
After once occuring, the acute disease caused by this bacterium has a strong tendency to develop into a systemic infection. Also a good prognosis for this disease can not be expected. Therefore this disease has come to be numbered as one of the most difficult to cure cured bacterial infectious diseases.
Infectious diseases caused by P. aeruginosa are generally difficult to cure for the following reasons:
(1) This bacterium exhibits a high resistance to almost all of the antibiotics which have been typically used.
(2) This bacterium tends to be resistant to recently developed antibiotics which are effective against P. aeruginosa.
(3) There is a high incidence of infectious diseases caused by P. aeruginosa which can not be satisfactorily treated by chemotherapy using these antibiotics.
On the basis of the fact that there is a limit to the chemotherapy of infectious diseases caused by P. aeruginosa performed using antibiotics, several attempts have been made to develop vaccines or infection-protective agents which are prepared from cell components of P. aeruginosa and used to increase the ability of the host to protect itself against P. aeruginosa.
For instance, the polyvalent vaccine PEV-01 protective against all serotypes of P. aeruginosa was prepared by purifying the superficial antigen of each serotype of P. aeruginosa (specific antigen for each serotype) and mixing the purified superficial antigens (Lancet II; 977, 1979). After performing an attempt to clinically apply this polyvalent vaccine to burn patients, it was reported that this vaccine is protective against septicemia by P. aeruginosa infection.
However, the preparation of this polyvalent vaccine is complicated by mixing more than 10 antigens against different serotypes of P. aeruginosa. Besides, since the specific antigens of different serotypes which are components of this vaccine are so-called 0 antigens existing in the surface layers of cells of P. aeruginosa and are composed of lipopolysaccharides called endotoxin, this vaccine cause unavoidably local and systemic side effects such as intense pyrogenecity.
OEP (original endotoxin protein) principally composed of protein was isolated as a serological common antigen to P. aeruginosa by Homma et al. It was reported that OEP works as an protective antigen common to all serotypes of P. aeruginosa and can be used for vaccine (Jpn. J. Exp. Med.; 47, 393-402, 1977).
Homma et al. thought that this infection can not satisfactorily be protected by OEP alone and carried out each clinical experiment by a vaccine consisting of a mixture of toxoids prepared by combining OEP with two or three components among protease, elastase and exo toxoid from P. aeruginosa. Although it was reported that these vaccines showed good effect in some cases, they have not yet been put to practical use.
The other vaccines of P. aeruginosa include ribosome vaccines each having a specific effect against each serotype of the bacterium, pili vaccines characterized by adhering to the surface of membrane, and flagella vaccines which stop the movement of bacteria. However, all of these vaccines are still in the experimental stage. Therefore, it is no exaggeration to say that the appearance of excellent vaccines against P. aeruginosa infection is still desired.